IL-6 Gene Research Articles

Роль генетических факторов в вероятности развития сахарного диабета 2-го типа

Type 2 diabetes mellitus (DM2) is the ninth leading cause of worldwide mortality. To predict likelihood of the disease and its unfavorable clinical course with developing complications, it is necessary to consider genetic and molecular factors of DM2 pathogenesis. Therefore, the aim of this review was to analyze the role that belongs to genetic factors in molecular mechanisms of DM2 development and to establish the most significant single nucleotide polymorphisms (SNP) in DM2 pathogenesis. The authors have analyzed literature sources found in such databases as CYBERLENINKA, E-library, and National Center for Biotechnology Information over the last 10 years as well as the integrated database GeneCards. By now, Genome-Wide Association Studies (GWAS) have identified about 100 genes and more than 700 polymorphisms that influence DM2 risks and its likelihood. Classifications of candidate genes with their effects and expression being limited by external and internal transcription factors are rather tentative. Literature analysis has established certain ambiguousness of the role that belongs to genetic markers in DM2 pathogenesis. It is advisable to add new genetic markers of the PPARγ, TLR4, IRS and IL-6 genes to the existing test-systems. This will increase the likelihood of detecting hereditary predisposition to diabetes mellitus according to the key molecular-genetic mechanisms of its development and ensure implementation of relevant measures aimed at preventing the disease and early identification of genetic risk groups.

Mixture toxic mechanism of phoxim and prochloraz in the hook snout carp Opsariichthysbidens

Pesticides are usually found as mixtures in surface water bodies, even though their regulation in aquatic ecosystems is usually approached individually. In this context, this work aimed to investigate the enzymatic- and transcriptional-level responses after the mixture exposure of phoxim (PHX) and prochloraz (PRC) in the livers of hook snout carp Opsariichthys bidens. These data exhibited that co-exposure to PHX and PRC induced an acute synergistic impact on O. bidens. The activities of catalase (CAT), superoxide dismutase (SOD), carboxylesterase (CarE), and caspase3 varied significantly in most of the individual and combined challenges relative to basal values, indicating the activation of oxidative stress, detoxification dysfunction, as well as cell apoptosis. Besides, the transcriptional levels of five genes (gst, erα, mn-sod, cxcl-c1c, and il-8) exhibited more pronounced changes when subjected to combined pesticide exposure in contrast to the corresponding individual compounds. The findings revealed the manifestation of endocrine dysfunction and immune disruption. These results underscored the potential biochemical and molecular toxicity posed by the combination of PHX and PRC to O. bidens, thereby contributing to a deeper comprehension of the ecological toxicity of pesticide mixtures on aquatic organisms. Importantly, the concurrent presence of PHX and PRC might exacerbate hepatocellular damage in hook snout carps, potentially attributable to their synergistic toxic interactions. This study underscored the toxicological potency inherent in the co-occurrence of PHX and PRC in influencing fish development, thereby offering valuable insights for the risk assessment of pesticide mixtures and the safeguarding of aquatic organisms.

Arterial stiffness and genetic polymorphism of some cytokines in normotensive patients with ankylosing spondylitis

Aim of the study was to identify the incidence of arterial stiffness in normotensive patients with ankylosing spondylitis (AS) in the Trans-Baikal region, to study polymorphism of genes for some cytokines and prognostic factors for increased arterial stiffness in this disease. Material and methods. We examined 100 patients with AS, natives of the Transbaikal region, HLA-В27 positive and 100 healthy controls, HLA-B27 negative; all included in the study were Caucasian. Arterial hypertension was an exclusion criterion. Determination of single nucleotide polymorphisms of the genes IL1B (‒31T/C, rs1143627), IL10 (‒592C/A, rs1800872), IL10 (‒819C/T, rs1800871), TNF (‒308G/A, rs1800629) was carried out in all patients with AS and healthy individuals. 74 patients with AS and 40 patients in the control group underwent applanation tonometry using SphygmoCor (AtCor Medical, Australia). Results. Pulse wave velocity on the carotid-femoral segment in patients with AS was 6.5 [4.1; 11.7] m/s, in the control group – 5.2 [3.9; 7.0] m/s (p = 0.0001). In 18 patients with AS (24.32 %) it was more than the age norm, these patients made up the group with elevated arterial stiffness. In patients with AS, carriage of the homozygous AA genotype of the IL10 gene (rs1800872, ‒592C/A) was 2.18 times more common, the homozygous GG genotype of the TNF gene (rs1800629, ‒308G/A) was 1.23 times more common, and the heterozygous ST genotype of the IL10 gene (rs1800871, ‒819C/T) was 1.5 times more common than in the control group. Prognostic factors for increased arterial stiffness in patients with AS were carriage of the IL10 rs1800871 polymorphism, age, and the radiological stage of changes in the sacroiliac joints. Conclusions. Increased arterial stiffness was detected in 24.3 % of normotensive patients with AS. The CT genotype of the IL10 gene (rs1800871, ‒819C/T), AA genotype of the of the IL10 gene (rs1800872, ‒592C/A), the G allele and the GG genotype of the TNF gene (rs1800629, позиция ‒308G/A) are associated with the development of AS in Caucasians. Multivariate regression analysis identified clinical and genetic factors that predict an increase in arterial stiffness in patients with AS, natives of the Trans-Baikal Territory.

Effects of Bryophyllum pinnatum on Dysfunctional Autophagy in Rats Lungs Exposed to Zinc Oxide Nanoparticles

Lung inflammation as a result of exposure to toxicants is a major pathological problem. Autophagy (AP) is a process of cell self-digestion and can be disrupted by environmental toxicants, leading to oxidative stress, inflammation and cellular damage. Bryophyllum pinnatum (Lam.) Oken has been used in folklore medicine to manage pathological abnormalities, including inflammation, but mechanisms remain unclear. This work investigated the effects of Bryophyllum pinnatum ethanol leaf extract (BP) on dysfunctional AP in the lungs of Wistar rats exposed to zinc oxide nanoparticles (ZONPs). The experimental rats were orally administered ZONPs for seven days (10 mg/kg). Some exposed rats were post-treated with BP (62.5 and 125 mg/kg) through oral gavage. Oxidative stress, inflammation, and apoptotic and autophagic parameters were assessed using biochemical assay and gene expression methods. Several indices of pulmonary damage were also evaluated. PCR analysis suggested that ZONP downregulated the expression of pro-autophagy-related genes (Beclin 2, ATG5, DAPK, and FOXP3) and upregulated the expression of the TNF-alpha, NF-Kb, LC3 and Bcl2 genes. In contrast, BP significantly (p < 0.0001) reversed ZONP-induced pulmonary toxicity and oxidative stress. It reduced MDA levels and increased SOD, CAT, GSH and GPxD activities. BP significantly (p < 0.0001) downregulated the expressions of proinflammatory genes (IL-6 and JNK) and upregulated the expressions of IL-10, CAT and SOD genes in ZONP-exposed rats. BP restored the lung’s histoarchitectural structure after ZNOP-induced distortion. The results suggested that BP has antioxidant and anti-inflammatory properties, and could effectively restore ZNOP-induced dysfunctional AP in the lungs of Wistar rats.

Characterization of ibrutinib's effects on the morphology, proliferation, phenotype, viability, and anti-inflammatory potential of adipose-derived mesenchymal stromal cells

Ibrutinib (IB) is a tyrosine kinase inhibitor (TKI) that has immunomodulatory action and can be used as second-line therapy for steroid-refractory or steroid-resistant chronic Graft versus Host Disease (cGVHD). Mesenchymal stromal cells (MSCs) are distributed throughout the body and their infusion has also been explored as a second-line therapeutic alternative for the treatment of cGVHD. Considering the currently unknown effects of IB on endogenous MSCs, as well as the possible combined use of IB and MSCs for cGVHD, we investigated whether adipose tissue-derived MSCs present IB-targets, as well as the consequences of treating MSCs with this drug, regarding cell viability, proliferation, phenotype, and anti-inflammatory potential. Interestingly, we show for the first time that MSCs express several IB target genes. Also of note, the treatment of such cells with this TKI elevated the levels of CD90 and CD105 surface proteins, as well as VCAM-1. Furthermore, IB-treated MSCs presented increased mRNA expression of the anti-inflammatory genes PD-L1, TSG-6, and IL-10. However, continued exposure to IB, even at low doses, compromised the viability of MSCs. These data indicate that the use of IB can stimulate an anti-inflammatory profile in MSCs, but also that a continued exposure to IB can compromise MSC viability over time.

Shedding reduction and immunity modulation in piglets with an inactivated Mycoplasma hyopneumoniae vaccine encapsulated in nanostructured SBA-15 silica

Mycoplasma (M.) hyopneumoniae is a primary etiological agent of porcine enzootic pneumonia (PEP), a disease that causes significant economic losses to pig farming worldwide. Current commercial M. hyopneumoniae vaccines induce partial protection, decline in preventing transmission of this pathogen or inducing complete immunity, evidencing the need for improving vaccines against PEP. In our study, we aimed to test the effectiveness of the SBA-15 ordered mesoporous silica nanostructured particles as an immune adjuvant of a vaccine composed of M. hyopneumoniae strain 232 proteins encapsulated in SBA-15 and administered by intramuscular route in piglets to evaluate the immune responses and immune-protection against challenge. Forty-eight 24-day-old M. hyopneumoniae-free piglets were divided into four experimental groups with different protocols, encompassing a commercial vaccine against M. hyopneumoniae, SBA-15 vaccine, SBA-15 adjuvant without antigens and a non-immunized group. All piglets were challenged with the virulent strain 232 of M. hyopneumoniae. Piglets that received the SBA-15 and commercial vaccine presented marked immune responses characterized by anti-M. hyopneumoniae IgA and IgG antibodies in serum, anti-M. hyopneumoniae IgA antibodies in nasal mucosa and showed an upregulation of IL-17 and IL-4 cytokines and downregulation of IFN-γ in lungs 35 days post-infection. Piglets immunized with SBA-15 vaccine presented a reduction of bacterial shedding compared to piglets immunized with a commercial bacterin. In addition, piglets from SBA-15 adjuvant suspension group presented increased IL-17 gene expression in the lungs without involvement of Th1 and Th2 responses after challenge. These results indicated that SBA-15 vaccine induced both humoral and cell-mediated responses in the upper respiratory tract and lungs, first site of replication and provided protection against M. hyopneumoniae infection with a homologous strain with reduction of lung lesions and bacterial shedding. Finally, these results enhance the potential use of new technologies such as nanostructured particles applied in vaccines for the pig farming industry.

Cytotoxicity, pro-inflammatory cytokines gene expression and antioxidant activity of Acmella oleracea extract treated with active charcoal

This work reports for the first time the evaluation of the cytotoxicity and inflammatory potential of Acmella oleracea extract treated with active charcoal in THP-1 monocytes. A. oleracea flower ethanolic extract was treated with 4% activated charcoal (TCEE). Later, THP-1 human monocyte cytotoxicity assay was performed using resazurin fluorometric method. Gene expression of inflammatory cytokines in THP-1 cells were evaluated through RT-PCR by ΔΔCt method using IL-1β, IL-6, IL-8, and TNF genes primers. Finally, antioxidant assay was carried out with DPPH radical scavenging method. TCEE had a LD50 of 592.5 µg/mL and did not induce pro-inflammatory gene expression in THP-1 cells after 6 h of treatment. Lastly, TCEE (AA% of 69.4 ± 1.4%) and CEE (AA% of 63.0 ± 0.9%) showed moderate antioxidant activity. A. oleracea treated flower extract showed low cytotoxicity in THP-1 monocytes and does not induce inflammation in THP-1 cells, in addition to presenting antioxidant potential.

Expression of miR-155 in monocytes of people with migraine: association with phenotype, disease severity and inflammatory profile

BackgroundmiR-155 is involved in the generation and maintenance of inflammation and pain, endothelial function and immune system homeostasis, all functions that are relevant for migraine. The present study aims to assess the levels of miR-155 in migraine subtypes (episodic and chronic) in comparison to age- and sex-matched healthy controls.MethodsThis is a cross-sectional, controlled, study involving three study groups: I) episodic migraine (n = 52, EM), II) chronic migraine with medication overuse (n = 44, CM-MO), and III) healthy controls (n = 32, HCs). We assessed the interictal gene expression levels of miR-155, IL-1β, TNF-α, and IL-10 in peripheral blood monocytes using rtPCR. The monocytic differentiation toward the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes was assessed in circulating monocytes with flow cytometry analysis and cell sorting.ResultsmiR-155 gene expression was higher in CM-MO group (2.68 ± 2.47 Relative Quantification - RQ) when compared to EM group (1.46 ± 0.85 RQ, p = 0.006) and HCs (0.44 ± 0.18 RQ, p = 0.001). In addition, miR-155 gene expression was higher in EM group when compared to HCs (p = 0.001). A multivariate analysis confirmed the difference between EM and CM-MO groups after correction for age, sex, smoking habit, preventive treatment, aura, presence of psychiatric or other pain conditions. We found higher gene expression of IL-1β, TNF-α, and lower gene expression of IL-10 in migraine participants when compared to HCs (p = 0.001 for all comparisons). TNF-α and IL-10 genes alterations were more prominent in CM-MO when compared to EM participants (p = 0.001). miR-155 positively correlated with IL-1β (p = 0.001) and TNF-α (p = 0.001) expression levels. Finally, in people with CM-MO, we described an up-regulated percentage of events in both M1 and M2 monocytic profiles.ConclusionsOur study shows for the first time a specific profile of activation of miR-155 gene expression levels in monocytes of selected migraine subpopulations, more pronounced in subjects with CM-MO. Interestingly, mir-155 expression correlated with markers of activation of the inflammatory and immune systems. The CM-MO subpopulation showed a peculiar increase of both pro-inflammatory and anti-inflammatory monocytes which worths further investigation.Trial registrationwww.clinicaltrials.gov. (NCT05891808).

Association of Interleukin-6 gene (rs1800795) variant with waist-hip-ratio and Insulin resistance: A cross-sectional study in adult women

Obesity is a major contributing factor to metabolic disorders and public health problems worldwide. The goal of the current study was to determine if the Interleukin-6 gene rs1800795 variant is linked to waist-hip-ratio (WHR) and insulin resistance (IR) in North Indian adult women. The WHO guidelines were followed by 37 women who had a WHR &gt;0.85 and 35 women who had a WHR &lt;0.85, out of the 72 women who took part in the study. Every adult woman underwent anthropometric measures. Fasting blood glucose, serum Insulin, lipid levels, and IL-6 levels were measured, and IR was computed. The RFLP technique was used to polymorphise the IL-6 gene (174 G&gt;C) variant. The study group's Insulin, HOMA-IR, BMI, lipid profile, TC/HDL ratio, HDL/LDL ratio, and serum IL-6 level were shown to differ significantly from the control. The percentage frequency of the IL-6 mutant genotype GC+CC (89.19%) and mutant allele C (75.68%) was higher in the study group (WHR &gt;0.85). According to the findings, WHR, TC, TG, and HOMA-IR were substantially correlated (all p &lt;0.05) with the mutant genotype GC+CC of the IL-6 174 G&gt;C gene. This study indicates that the IL-6 rs1800795 gene (174 G&gt;C) variant was substantially linked with metabolic risk variables, such as WHR and HOMA-IR.

Identification and Analysis of Differentially Expressed Genes Associated with Ferroptosis an d HIV in PASMCs Based on Bioinformatics.

HIV-associated pulmonary arterial hypertension (HIV-PAH), a rare and fatal condition within the pulmonary arterial hypertension spectrum, is linked to HIV infection. While ferroptosis, an iron-dependent cell death form, is implicated in various lung diseases, its role in HIVPAH development remains unclear. Leveraging Gene Expression Omnibus data, we identified differentially expressed genes (DEGs) in pulmonary arterial smooth muscle cells, including HIV-related DEGs (HIV-DEGs) and ferroptosis-related HIV-DEGs (FR-HIV-DEGs). PPI network analysis of FR-HIV-DEGs using CytoHubba in Cytoscape identified hub genes. We conducted functional and pathway enrichment analyses for FR-HIV-DEGs, HIV-DEGs, and hub genes. Diagnostic value assessment of hub genes utilized ROC curve analysis. Key genes were further screened, and external validation was performed. Additionally, we predicted a potential ceRNA regulatory network for key genes. 1372 DEGs were found, of which 228 were HIV-DEGs, and 20 were FR-HIV-DEGs. TP53, IL6, PTGS2, IL1B (downregulated), and PPARG (upregulated) were the five hub genes that were screened. TP53, IL6, and IL1B act as ferroptosis drivers, PTGS2 as a ferroptosis marker, and PPARG as a ferroptosis inhibitor. Enrichment analysis indicated biological processes enriched in "response to oxidative stress" and pathways enriched in "human cytomegalovirus infection." Key genes IL6 and PTGS2 exhibited strong predictive value via ROC curve analysis and external validation. The predicted ceRNA regulatory network identified miRNAs (has-mir-335-5p, has-mir-124-3p) targeting key genes and lncRNAs (XIST, NEAT1) targeting these miRNAs. This study advances our understanding of potential mechanisms in HIV-PAH pathogenesis, emphasizing the involvement of ferroptosis. The findings offer valuable insights for future research in HIV-PAH.

Elucidating the effect of dietary neem (Azadirachta indica) on growth performance, haemato-biochemical, immunonological response, and anti-pathogenic capacity of Nile tilapia juveniles.

This investigation attempts to evaluate the effect of diet additives via aqueous or ethanolic herbal extracts from Azadirachta indica leaves on Nile tilapia, Oreochromis niloticus. Five dietary categories were assigned to the fish: the first category (N1, with no extract) was kept under control conditions; two categories contained aqueous extract (N2 (1.0g/kg) and N3 (2.0g/kg); and two categories contained ethanolic extract, N4 (1.0g/kg) and N5 (2.0g/kg), with each group being fed for 60 days. After the feeding trial, Aeromonas hydrophila was injected intraperitoneally into fish for 14 days; fish mortality was recorded during this period. The results showed that the fish-fed dietary A. indica significantly improved growth performance and intestinal health (digestive enzymes and intestinal morphology), especially in the N4 and N5 categories. However, N4 and N5 categories demonstrated a significant decrease in AST and ALT activities and an increase in total protein, serum albumin, globulin, growth hormone (GH), leptin hormone (LEP), hemoglobin, white blood cells, and hematocrit (P < 0.05) in comparison with the control category (N1). Compared to the control category, the N4 and N5 categories have revealed a significant reduction in MDA activity and improvements in immunological activities (lysozyme, complement C3, and nitric oxide) and antioxidant enzymes (CAT, SOD, and GPX). Moreover, in tilapia-fed A. indica, the expression of IL-8, IL-1β, and Nf-κb genes was downregulated partially in the N4 and N5 categories than the control category. In contrast, the lysozyme, C3, GPX, and CAT genes were upregulated partially at N4 and N5 compared to the control category. Following the bacterial challenge, fish in the N4 and N5 categories also displayed the lowest fish mortality compared to the control category. The ethanolic extract displayed a more potent resistance against the parasite Cichlidogyrus tilapia in vitro than the aqueous and control categories, partially at 2g/L. According to these findings, an ethanolic neem extract (2.0g/kg feed) activates the immune system and antioxidant response in Nile tilapia fingerlings, improving growth and fish resistance to parasitic and bacterial infections.

Early- and life-long intake of dietary advanced glycation end-products (dAGEs) leads to transient tissue accumulation, increased gut sensitivity to inflammation, and slight changes in gut microbial diversity, without causing overt disease

Dietary advanced glycation end-products (dAGEs) accumulate in organs and are thought to initiate chronic low-grade inflammation (CLGI), induce glycoxidative stress, drive immunosenescence, and influence gut microbiota. Part of the toxicological interest in glycation products such as dietary carboxymethyl-lysine (dCML) relies on their interaction with receptor for advanced glycation end-products (RAGE). It remains uncertain whether early or lifelong exposure to dAGEs contributes physiological changes and whether such effects are reversible or permanent. Our objective was to examine the physiological changes in Wild-Type (WT) and RAGE KO mice that were fed either a standard diet (STD − 20.8 ± 5.1 µg dCML/g) or a diet enriched with dCML (255.2 ± 44.5 µg dCML/g) from the perinatal period for up to 70 weeks. Additionally, an early age (6 weeks) diet switch (dCML→STD) was explored to determine whether potential harmful effects of dCML could be reversed. Previous dCML accumulation patterns described by our group were confirmed here, with significant RAGE-independent accumulation of dCML in kidneys, ileum and colon over the 70-week dietary intervention (respectively 3-fold, 17-fold and 20-fold increases compared with controls). Diet switching returned tissue dCML concentrations to their baseline levels. The dCML-enriched diet had no significative effect on endogenous glycation, inflammation, oxidative stress or senescence parameters. The relative expression of TNFα, VCAM1, IL6, and P16 genes were all upregulated (∼2-fold) in an age-dependent manner, most notably in the kidneys of WT animals. RAGE knockout seemed protective in this regard, diminishing age-related renal expression of TNFα. Significant increases in TNFα expression were detectable in the intestinal tract of the Switch group (∼2-fold), suggesting a higher sensitivity to inflammation perhaps related to the timing of the diet change. Minor fluctuations were observed at family level within the caecal microbiota, including Eggerthellaceae, Anaerovoracaceae and Marinifilaceae communities, indicating slight changes in composition. Despite chronic dCML consumption resulting in higher free CML levels in tissues, there were no substantial increases in parameters related to inflammageing. Age was a more important factor in inflammation status, notably in the kidneys, while the early-life dietary switch may have influenced intestinal susceptibility to inflammation. This study affirms the therapeutic potential of RAGE modulation and corroborates evidence for the disruptive effect of dietary changes occurring too early in life. Future research should prioritize the potential influence of dAGEs on disease aetiology and development, notably any exacerbating effects they may have upon existing health conditions.

In vitro evidence of antioxidant and anti-inflammatory effects of a new nutraceutical formulation explains benefits in a clinical setting of COPD patients.

Background and Aim: Increased oxidative stress within the airways is associated to epithelial damage and amplification of inflammatory responses that in turn contribute to Chronic Obstructive Pulmonary Disease (COPD) progression. This study was aimed to identify whether a new formulation of N-acetylcisteine (NAC), carnitine, curcumin and B2 vitamin could counteract oxidative stress and downstream pro-inflammatory events promoted by cigarette smoke extract (CSE) exposure in primary bronchial epithelial cells (PBEC), both submerged/undifferentiated (S-PBEC) and cultured at the air-liquid interface (ALI-PBEC). Methods: PBEC were exposed to CSE with/without the new formulation or NAC alone and ROS production, IL-8 and IL-6 gene expression and protein release were evaluated. Results: CSE increased ROS, IL-8 and IL-6 gene expression and protein release and the new formulation counteracted these effects. NAC alone was not effective on IL-8 and IL-6 release. The effects of a similar nutraceutical formulation were evaluated in COPD patients treated for six months. The results showed that the treatment reduced the concentration of IL-8 in nasal wash and improved quality of life. Conclusion: The tested formulation, exerting antioxidant and anti-inflammatory effects, can preserve airway epithelial homeostasis and improve clinical symptoms in COPD.

Genetic polymorphisms in external apical root resorption and orthodontic tooth movements: A systematic review.

External apical root resorption (EARR) is characterized by permanent loss of dental structure at the root apex. This study aimed to systematically review gene polymorphisms associated with EARR in orthodontic patients. Electronic database searches were performed across several databases. This systematic review included 21 studies. Outcome measures were based on tooth dimensions observed on radiographs obtained before and after treatment. Polymorphisms in the following genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis: purinergic-receptor-P2X, ligand-gated ion channel 7 (P2RX7), caspase-1/interleukin-converting enzyme (CASP1/ICE), caspase-5 (CASP5), IL-1beta (IL1B), IL-1alpha (IL1A), interleukin-1 receptor antagonist gene (IL1RN), tissue non-specific alkaline phosphatase (TNSALP), tumor necrosis factor-alpha (TNFα), tumor necrosis factor receptor superfamily gene member 11a (TNFRSF11A), secreted phosphoprotein 1 (SPP1), tumor necrosis factor receptor superfamily gene member 11b (TNFRSF11B), interleukin 17A (IL17), interleukin 6 (IL6), receptor activator of nuclear factor-kappa B (RANK), osteoprotegerin (OPG), stromal antigen 2 (STAG2), vitamin D receptor (VDR), cytochrome P450 family 24 subfamily A member 1 (CYP24A1), cytochrome P450 family 27 subfamily B (CYP27B1), group-specific component (GC), and interleukin-1 receptor-associated kinases 1 (IRAK1). Almost all studies suggested that IL1 gene is associated with EARR. Additionally, P2RX7 may be an important factor contributing to the etiopathogenesis of EARR. TNFRSF11A, SPP1, IL1RN, IL6, TNFRSF11B, STAG2, VDR, IRAK1, IL-17, CASP1/ICE and CASP5 have been identified in isolated studies. Further observational studies are needed to better explain the association between these genes and EARR.

A specific GAGTT insertion/deletion variation in the IL-10 gene promoter alters the disease resistance of grass carp

IL-10, an anti-inflammatory cytokine, plays crucial roles in the context of infectious inflammatory diseases, whose gene variations and expression are tightly linked to disease resistance in animals. However, there is limited research on the genetic variations governing IL-10 expression and the underlying effects in fish. In this study, we identified a GAGTT insertion/deletion (Ins/Del) variation within the IL-10 gene promoter and analyzed the effects of this variation on IL-10 expression, inflammatory response and its association with disease resistance in grass carp. With dual luciferase reporter assays, we demonstrated that the GAGTT Ins/Del variation significantly altered the IL-10 promoter activity in grass carp. DNA pull-down combined with mass spectrometry revealed that the spectrum of transcription factors that bind to IL-10 promoter variants caused by GAGTT Ins/Del variation was quite different. Moreover, three representative transcription factors, JunD/AP-1, p50/NF-κB, and HMGB1, differentially transactivated grass carp IL-10 promoter variants, as confirmed by western blotting and dual luciferase reporter assays. Using the GAGTT/− genotype of the heterozygous grass carp parents, we obtained full-sib family offspring of the GAGTT/GAGTT, GAGTT/−, and −/− genotypes. During grass carp reovirus (GCRV) infection, these three IL-10 genotypes of grass carp offspring displayed different survival rates. Importantly, grass carp with the GAGTT/− genotype had greater survival than those with the other two genotypes after GCRV infection. Furthermore, the results indicated that the improved intestinal inflammation at 1 d post-GCRV infection and enhanced immunocompetence in the spleen at 5 d post-GCRV infection may contribute to the disease resistance of grass carp with the GAGTT/− genotype. Overall, this study offers new insight into the inflammatory and immune regulatory mechanisms specific to IL-10 from a genetic perspective in fish and may provide a valuable molecular marker for breeding disease-resistant grass carp.

Influenza A virus infection activates caspase-8 to enhance innate antiviral immunity by cleaving CYLD and blocking TAK1 and RIG-I deubiquitination

Caspase-8, an aspartate-specific cysteine protease that primarily functions as an initiator caspase to induce apoptosis, can downregulate innate immunity in part by cleaving RIPK1 and IRF3. However, patients with caspase-8 mutations or deficiency develop immunodeficiency and are prone to viral infections. The molecular mechanism underlying this controversy remains unknown. Whether caspase-8 enhances or suppresses antiviral responses against influenza A virus (IAV) infection remains to be determined. Here, we report that caspase-8 is readily activated in A549 and NL20 cells infected with the H5N1, H5N6, and H1N1 subtypes of IAV. Surprisingly, caspase-8 deficiency and two caspase-8 inhibitors, Z-VAD and Z-IETD, do not enhance but rather downregulate antiviral innate immunity, as evidenced by decreased TBK1, IRF3, IκBα, and p65 phosphorylation, decreased IL-6, IFN-β, MX1, and ISG15 gene expression; and decreased IFN-β production but increased virus replication. Mechanistically, caspase-8 cleaves and inactivates CYLD, a tumor suppressor that functions as a deubiquitinase. Caspase-8 inhibition suppresses CYLD cleavage, RIG-I and TAK1 ubiquitination, and innate immune signaling. In contrast, CYLD deficiency enhances IAV-induced RIG-I and TAK1 ubiquitination and innate antiviral immunity. Neither caspase-3 deficiency nor treatment with its inhibitor Z-DEVD affects CYLD cleavage or antiviral innate immunity. Our study provides evidence that caspase-8 activation in two human airway epithelial cell lines does not silence but rather enhances innate immunity by inactivating CYLD.

Photoaging of polystyrene-based microplastics amplifies inflammatory response in macrophages

The continuous release of municipal and industrial products into the environment poses a growing concern for public health. Among environmental pollutants, polystyrene (PS) stands out as a primary constituent of environmental plastic waste, given its widespread use and high production rates owing to its durability and user-friendly properties. The detection of polystyrene microparticles (PS-MPs) in various living organisms has been well-documented, posing a serious threat due to their potential passage into the human ecosystem. In this manuscript, we aimed to study the toxicological effects of low concentrations of pristine and photoaged PS-MPs in a murine macrophage cell line. To this purpose, PS-MPs were photoaged by indoor exposure to visible light to simulate environmental weathering due to solar irradiation (PS-MPs3h). Physical characterization revealed that the irradiation treatment results in particle degradation and the possible release of nanoparticles. Monocultures of the RAW264.7 cell line were then exposed to PS-MPs and PS-MPs3h at concentrations comparable to experimental measurements from biological samples, to assess cytotoxicity, intracellular oxidative stress, primary genotoxicity, and inflammatory effects. Significant toxicity-related outcomes were observed in cells treated with both pristine PS-MPs and PS-MPs3h even at low concentrations (0,10 μg/ml and 1 μg/ml). PS-MPs3h exhibited greater adverse effects compared to PS-MPs, including reduced cell viability, increased ROS production, elevated DNA damage, and upregulation of IL-6 and NOS2 gene expression. Therefore, we can conclude that changes induced by environmental aging in the physicochemical composition of PS microplastics play a crucial role in the adverse health outcomes associated with microplastic exposure.

Preventive and reparative potentials of heat-inactivated and viable commensal Bacillus pumilus SE5 in ameliorating the adverse impacts of high soybean meal in grouper (Epinephelus coioides)

Probiotic Bacillus pumilus SE5, heat-inactivated (HSE5) or active (ASE5), were supplemented to high soybean meal (HSM) (36 %) diet at whole term (0–56 days) and middle term (29–56 days) to investigate the preventing and repairing effects of B. pumilus SE5 in ameliorating the adverse effects of HSM in Epinephelus coioides. The results suggested that the HSM significantly decreased the weight gain rate (WGR), specific growth rate (SGR), and increased the feed conversion rate (FCR) at day 56 (P < 0.05), while HSE5 and ASE5 promoted the growth performance. The HSE5 and ASE5 showed preventive and reparative functions on the antioxidant capacity and serum immunity, with significantly increased the total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX) activities, and reduced malondialdehyde (MDA) level, and increased acid phosphatase (ACP), alkaline phosphatase (AKP), immunoglobulin M (IgM) and complement 3 (C3). The HSM impaired the intestinal health (destroyed the intestinal structure, significantly increased the contents of serum D-lactic acid and diamine oxidase, and reduced the expressions of claudin-3 and occludin), while HSE5 and ASE5 improved them at whole term and middle term. The HSM impaired the intestinal microbiota and reduced its diversity, and the HSE5 or ASE5 improved the intestinal microbiota (especially at whole term). HSE5 and ASE5 improved the intestinal mRNA expressions of anti-inflammatory genes (il-10 and tgf-β1) and reduced the expressions of pro-inflammatory genes (il-1β, il-8, il-12), and promoted the expressions of humoral immune factor-related genes (cd4, igm, mhcII-α) and antimicrobial peptide genes (β-defensin, epinecidin-1 and hepcidin-1), and decreased the expressions of NF-κB/MAPK signaling pathway-related genes (ikk-α, nf-κb, erk-1), and improved the expressions of MAPK signaling pathway-related gene p38-α (P < 0.05). In conclusion, the heat-inactivated and active B. pumilus SE5 effectively prevented and repaired the suppressive effects of soybean meal in E. coioides, which underscored the potential of B. pumilus SE5 as a nutritional intervention agent in HSM diet in aquaculture.

Identification of the IL-13 gene rs20541 single nucleotide polymorphism and its association with renal cell carcinoma in Iraqi patients

Identification of the IL-13 gene rs20541 single nucleotide polymorphism and its association with renal cell carcinoma in Iraqi patients

Yinxie I Formula attenuates imiquimod-induced psoriasis-like skin inflammation via IL-23/IL-17 axis

Psoriasis is considered a chronic inflammatory skin disorder characterized by keratinocytes hyperproliferation. The IL-23/IL-17 immune pathway has been substantiated in numerous studies to be closely associated with psoriasis progression. Yinxie I Formula is a traditional Chinese medicine made from 9 herbal medicines, which has excellent clinical efficacy in psoriasis. However, to date, the mechanism of action of Yinxie I Formula against psoriasis remains unknown. In this perspective, we discuss the efficacy of Yinxie I Formula in mice with imiquimod (IMQ) induced psoriasis. Yinxie I Formula significantly reduced the area of skin lesions and the inflammatory response in mice with psoriasis. Furthermore, Yinxie I Formula alleviated the expression levels of inflammation-related genes IL-6, IL-17 A, IL-22, IL-23, TNF-α and IL-23, IL-18, IL-6 and IL-1β-related proteins and alleviated the abnormal surge of dendritic cells, macrophages and T cells in the skin and spleen. Meanwhile we found that Yinxie I Formula reduced the release of NO, TNF-α, IL-1β and IL-23 in lipopolysaccharide-induced mouse macrophage RAW264.7 cell line. The results suggest that the therapeutic mechanism of Yinxie I Formula may also be correlated with the STAT signaling pathway. We further analyzed the active ingredient of Yinxie I Formula, Buddleoside, which may be the main substance that exerts the therapeutic effect. In conclusion, we have investigated that Yinxie I Formula attenuates the IMQ-induced inflammatory response in psoriasis by inhibiting the IL-23/IL-17 axis, which lays the foundation for the antipsoriasis mechanism and provides a theoretical basis for the clinical promotion of Yinxie I Formula.